The microenvironment in which cancer develops is crucial both to basic cancer biology and the development of novel therapeutic concepts. Effective in vivo models in whole animals are needed to address these issues and to assess adverse side effects of cancer therapies including radiation. In preliminary work it was stablished that zebrafish embryos provide a facile system to assess modulation of the radiation response in vivo. The applicant will extend these studies to critically examine the functional contribution of distinct p53 Family members to the radiation response in normal tissues and organs. This work will be performed by using state-of-the-art methods of downregulating gene expression or function and has important translational ramifications.